Clinicians managing people with idiopathic pulmonary fibrosis (IPF) are left with few options once the disease seriously progresses despite pirfenidone treatment. Now, a study shows that continuing treatment is the best way to move forward, as it is likely to prevent an even greater decline in lung function and keep death at bay.
The study, “Effect of continued treatment with pirfenidone following clinically meaningful declines in forced vital capacity: analysis of data from three phase 3 trials in patients with idiopathic pulmonary fibrosis,“ was published in the journal Thorax.
While the recent approval of the IPF drugs pirfenidone (Esbriet) and nintedanib (Ofev) has transformed the treatment of the lung disease, neither is a cure, and there are no second-line options in case a patient experiences meaningful disease progression.
Further, no guidance existed regarding questions of what constitutes a suboptimal treatment response or how these patients should be managed.
The study from the Inova Fairfax Hospital, Virginia, analyzed data from the ASCEND and CAPACITY clinical trials, involving a total of 1,247 patients, of whom 623 received pirfenidone and 624 received placebo.
To investigate the variability of disease progression, the researchers first analyzed data only from placebo-treated patients. They explored the relationship between changes in forced vital capacity (FVC) from initiation of treatment to six months with the changes recorded between month six and month 12.
Findings that included a more detailed analysis of 50 patients showed that disease progression was highly variable, and it was not possible to predict how the disease would develop based on measurements during the first six months.
Researchers then looked at the patients in both the placebo and pirfenidone groups whose disease had worsened by 10 percent or more. About twice the number of patients experienced a substantial worsening in the placebo group compared to the pirfenidone group in the first six months — 10.9 percent compared to 5.5 percent.
During the following six months, fewer patients in the treatment group experienced a 10 percent or higher decline in FVC, or death — 5.9 percent in the pirfenidone group compared to 27.9 percent in the placebo group. One patient died in the treated group and 14 in the placebo group.
The 10 percent cutoff value has been used to define treatment failure in IPF, and guidelines for the diagnosis and management of IPF issued in 2011 by an expert committee — and endorsed by several international professional societies — stated that a 10 percent or higher decline in FVC was evidence of meaningful disease progression.
The study, however, clearly indicated that even when patients worsen by more than 10 percent while on pirfenidone treatment, continued treatment is still the best option, as it protects from further disease progression and death. The 10 percent limit might be a suitable outcome in clinical trials but should not be interpreted as treatment failure, the researchers said, as it is not possible to exclude even greater disease progression in patients refraining from treatment.